Impact of OCT1 on Metformin Tolerance
Research type
Research Study
Full title
Impact of OCT1 Genotype and OCT1 Inhibiting Drugs on an Individual's Tolerance of Metformin
IRAS ID
193662
Contact name
Ewan R Pearson
Contact email
Sponsor organisation
University of Dundee
Clinicaltrials.gov Identifier
Duration of Study in the UK
2 years, 3 months, 3 days
Research summary
Metformin is the first-line treatment for medical management of Type 2 Diabetes. Up to 25% of patients experience significant gastrointestinal symptoms and in approx 5%, side-effects result in the discontinuation of metformin. It would be of great clinical significance if the underlying cause of this intolerance was identified.
Recent data has highlighted a metformin transporter in the gut – Organic Cation Transporter 1(OCT1) – as a potential culprit for the variability in metformin tolerance. Across a diabetic population, up to one in four people were shown to have a single reduced function allele for OCT1, with approximately 8% having two reduced function alleles. This may increase the risk of the individual experiencing metformin-associated side-effects, potentially due to accumulation within the cells lining the intestine. We aim to show that loss of function of OCT1, either due to genetic variation or drug inhibition of OCT1, may lead to an increase in the symptoms associated with metformin intolerance.The study is being undertaken at the Clinical Research Centre in Ninewells Hospital, Dundee. We will recruit participants from GoDARTS (Genetics of Diabetes and Audit Research Tayside Study), GoSHARE, and Generation Scotland: Scottish Family Health Study. The participants will be healthy controls, i.e. nondiabetic, and recruited according to their genotype of OCT1 (information from GoDARTS), from the Tayside region. The volunteers will then enter a matched cross-over study with two treatment periods. Metformin is taken during both treatment periods alongside either Omeprazole (a proton pump inhibitor used to prevent excess stomach acid, known to interact with OCT1) or placebo. The metformin dose is increased gradually during each period, to a maximum tolerated dose. We expect to see a lower maximum tolerated dose in individuals with loss of function genotype, or in those taking concurrent omeprazole compared to placebo. The study will last approx. 9 weeks. Volunteers have 3 visits to the CRC, and weekly phone call interviews.
REC name
East of Scotland Research Ethics Service REC 1
REC reference
15/ES/0189
Date of REC Opinion
25 Nov 2015
REC opinion
Favourable Opinion